[unreadable] This is a resubmission of a competitive renewal grant application whose goal is to develop a unique 3D SPECT imaging technique using rotating multi-segment slant-hole (RMSSH) collimators. The major advantage for the innovative technique is its ability to provide substantial increase in detection efficiency for the same spatial resolution as compared to parallel-hole SPECT in imaging small organs such as breasts and heart. (For a 4- segment slant-hole collimator, the gain is -3 times higher than that of a standard parallel-hole collimator with the same resolution.) In addition, the technique allows fully 3D image reconstruction of RMSSH projection data acquired with the camera rotating over a limited angular range. The acquisition strategy is particularly suitable for imaging the breast and heart of very sick patients in NM clinics, emergency room and intensive care units. During the last 3 years, we have (1) designed, constructed and evaluated a RMSSH collimator for 3D imaging of the breast, (2) developed and evaluated new 3D analytical and iterative reconstruction algorithms for projection data acquired using a RMSSH collimator, (3) developed a Monte Carlo simulation software package that allows us to design and evaluate the instrumentation, data acquisition strategies and image reconstruction methods for RMSSH SPECT, and (4) performed experimental phantom studies that provide preliminary evaluation of RMSSH SPECT for clinical imaging of the breast and heart. In this renewal application, we propose to continue the development of RMSSH in breast imaging from theoretical, simulation and experimental to clinical studies. In addition, we propose extend the application of RMSSH SPECT to cardiac imaging of very sick patients in NM clinics, emergency room and intensive care units. This competitive renewal application has 6 specific aims. They are: (1) to design optimized MSSH and MSVSH collimators for breast and cardiac SPECT, (2) to develop 3D image reconstruction methods for RMSSH and RMSVSH SPECT that include correction for attenuation, collimator-detector blur and scatter, (3) to evaluate data acquisition strategies and image reconstruction methods for the two RMSSH SPECT imaging techniques of the breast and heart using phantom studies, (4) to evaluate the applications of the two RMSSH SPECT imaging techniques for the breast and heart using Hotelling and human observers on simulated data, (5) to evaluate the application of the two RMSSH SPECT techniques to clinical breast imaging, and (6) to evaluate the application of the two RMSSH SPECT techniques to clinical cardiac SPECT imaging. [unreadable] [unreadable]